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Biomedical subjects

M Klockars

Publications and source records attributed to M Klockars.

At least 19 recordsLinked to original sources

Tumour necrosis factor enhances the asbestos-induced production of reactive oxygen metabolites by human polymorphonuclear leucocytes (PMN).

We studied the effect of recombinant tumour necrosis factor-alpha (TNF-alpha) on the production of reactive oxygen metabolites (ROM) by human PMN exposed in vitro to chrysotile and crocidolite asbestos fibres, quartz dusts and opsonized zymosan. TNF caused a significant increase in ROM release by PMN, and significantly and dose-dependently amplified the ROM production induced by asbestos fibres. The amplification of ROM production by TNF can be of crucial importance in the process of lung inflammation and fibrogenesis in pneumoconioses.

Asbestos

Interferon-gamma and immunoglobulin enhance mineral dust-induced production of reactive oxygen metabolites by human macrophages.

The modulating effect of interferon-gamma (IFN-gamma) and polyclonal immunoglobulin (poly-Ig) on mineral dust-induced production of reactive oxygen metabolites (ROM) by human monocyte-derived macrophages was investigated using lucigenin-dependent chemiluminescence. Activation of the cell cultures with IFN-gamma enhanced the subsequent quartz- and asbestos-induced production of ROM, while the addition of poly-Ig only stimulated chrysotile asbestos-induced ROM production. The combination of IFN activation and the addition of poly-Ig to the reactions caused a 20-fold enhancement of the responses to chrysotile. As increased levels of IFN-gamma and immunoglobulins have been observed in patients with mineral dust-induced diseases, we suggest that "immunological activation" caused by, for example, autoimmune diseases or recurrent pulmonary infections might amplify the production of potentially tissue-injuring ROM by mononuclear phagocytes and may possibly determine the individual susceptibility to mineral dust-related disorders.

Asbestos

Serum adenosine deaminase in viral and bacterial pneumonia.

We measured the activity of serum adenosine deaminase (ADA) in paired sera from 171 military conscripts with radiographically verified pneumonia. Patient serum samples were selected on the basis of serologic analyses identifying as single etiologic agents Streptococcus pneumoniae in 29 patients, Haemophilus influenzae in 7, Mycoplasma pneumoniae in 43, adenovirus in 24, influenza A or B in 12, and parainfluenza in 5 patients. In 14 patients Neisseria meningitidis and in 31 Chlamydia spp were considered the main etiologic agent. Compared with a control group of 45 healthy men, the ADA activity in patients with pneumonia was significantly higher (p less than 0.001) in all patient groups except those with meningococcal pneumonia. The highest ADA levels were seen in patients with pneumonia caused by M pneumoniae (27.4 +/- 9.7 U/L), Chlamydia spp (26.3 +/- 9.1 U/L), and adenovirus (28.5 +/- 10.9 U/L) compared with the controls (11.1 +/- 3.0 U/L). In patients with meningococcal pneumonia, the ADA activity was significantly decreased (p less than 0.001). Serum ADA activity probably reflects differences in cellular immune response to different infectious agents. The ADA determinations may give corroborative information on the etiologic agent of pneumonia.

Adenosine Deaminase

Diagnostic value of cerebrospinal fluid adenosine deaminase determination.

We measured the activity of adenosine deaminase (ADA) in the cerebrospinal fluid of 3 patients with tuberculous meningitis, 38 with viral meningitis, 15 with bacterial meningitis, 5 with malignant lymphoma, 11 with cerebrovascular diseases and 13 with miscellaneous neurological disorders. The highest ADA activities were observed in patients with tuberculous meningitis (median 21.3 U/l, range 20.0-23.0) and lymphoma (13.0 U/l, range 4.0-25.0). The sensitivity of the test for diagnosing tuberculous meningitis was 100% and the specificity 99% when a cut-off value of 20.0 U/l was used. We conclude that determination of ADA in cerebrospinal fluid is useful for the diagnosis of tuberculous meningitis, but that high activity also can be seen in some other CNS disorders, e.g. lymphoma with meningeal involvement.

Adenosine Deaminase

Work load and individual factors affecting work ability among aging municipal employees.

The effects of work stressors, individual characteristics, symptoms, and diseases on work ability were studied among 4255 municipal employees. Work ability was assessed by a work ability index in two cross-sectional inquiries, one in 1981 and the other in 1985. The most impairing for work ability were mental symptoms and musculoskeletal disease. Among the work stressors, high physical demands at work, poor physical work environment, and lack of freedom were associated with impaired work ability. Muscular work, disturbing temperatures at the workplace, and lack of freedom particularly affected employees with disease, whereas poor work postures and role conflicts at work were particularly injurious for healthy employees. The worst situation was observed when a worker with many symptoms and disease was exposed to many different work stressors. Life satisfaction, sitting work posture, a good basic education, and physical exercise during leisure time were associated with good work ability.

Cardiovascular Diseases

Summary and recommendations of a project involving cross-sectional and follow-up studies on the aging worker in Finnish municipal occupations (1981-1985).

This report is a summary of the main findings of 15 studies comprising a multidisciplinary research project. Recommendations are also made on the basis of the findings, and they emphasize the following points: (i) work demands should change with age, (ii) work should be designed for unhealthy people, (iii) work ability should be promoted, (iv) work ability should be regularly monitored, (v) special attention to stress reactions is needed, (vi) knowledge of aging is needed, and (vii) action programs are needed.

Aging

Mortality, disability and changes in occupation among aging municipal employees.

During a four-year follow-up period the indicators of work load, individual factors, and stress reactions predicting mortality, disability, and change of occupation were studied. In 1981, 6257 active workers aged 44-58 years answered a questionnaire. The study was repeated in 1985 when 1% of the subjects had died, 9% had become disabled, and 5% had changed their occupation. These changes had occurred the most often in occupations which included muscular work, poor work postures, and a poor physical environment. The highest mortality rate was observed for the male installation and auxiliary workers who had reported the presence of cardiovascular, but no musculoskeletal, disease four years earlier. The highest disability rate was well predicted by a poor index of work ability. Major diseases leading to disability included malignant tumor, coronary artery disease, congestive heart failure, rheumatoid arthritis, bronchitis or bronchial asthma, and mental disease. Work-related stress reactions were associated with both mortality and disability.

Cardiovascular Diseases

Prevalence and incidence rates of diseases and work ability in different work categories of municipal occupations.

The purpose of this study was to determine the relationship between the health status and work ability of individuals representing a variety of municipal occupations. In both 1981 and 1985, 4255 employees answered a postal questionnaire. The subjects, aged 44-58 years in 1981, were grouped into physical, mental, or mixed physical and mental job categories. Occupational groups with a high disease prevalence in 1981 had a high, and occupational groups with a low disease prevalence in 1981 a low, disease incidence during the follow-up period. In 1985 every second subject suffered from a musculoskeletal disease. The highest disease prevalence was observed for physically demanding occupations and for men in work with mixed physical and mental demands. Female auxiliary workers, domestic helpers and cooks, and also male installation and transport workers, had the poorest health. The men and women in mental work had the best health and work ability.

Cohort Studies

Background and objectives of the Finnish research project on aging workers in municipal occupations.

In Finland, the proportion of 45- to 64-year-old people in the work force is expected to increase from 31.1 to 40.1% between 1980 and 2000. A multidisciplinary study was carried out to test the factors of work, health, work ability, functional capacity, and perceived strain as criteria for determining new concepts for retirement age. The first phase of the project comprised cross-sectional studies in which the age of the 6257 working subjects ranged from 45 to 58 years. The second phase covered a four-year follow-up of these same subjects. The main results of the 15 various studies are given in separate articles. Recommendations for improving the work and promoting the work ability of the aging worker have been made on the basis of the findings of the project.

Aged

Effect of retirement on health and work ability among municipal employees.

A questionnaire was sent to 6257 active employees, mean age 50.5 years, in 1981, and again in 1985, when 4255 of the workers were still actively working, 402 had retired because of age, and 468 had retired for medical reasons. After retirement, regardless of reason or previous work content, the prevalence of musculoskeletal diseases changed little among the women but increased markedly among the men retired from mental work. Among the men retired from mental work because of age, the prevalence of cardiovascular diseases increased after retirement. After disability pensioning the prevalence of cardiovascular diseases increased for both the men and the women. The prevalence of poor work ability increased in all the work categories irrespective of the type of retirement. Work ability did not improve after old-age pensioning, but health status was improved among the men and women in some occupational groups. Therefore light, part-time work should not be excluded for retired people.

Cardiovascular Diseases

Work-related stress symptoms of aging employees in municipal occupations.

The objective of the study was to investigate the relationship between stress symptoms and work stressors among aging employees in municipal occupations. The subjects were 1799 men and 2456 women aged 48-62 years and representing 40 different occupations. Stress reactions were identified on the basis of long-term cardiorespiratory, musculoskeletal, and psychological symptoms. Work stressors were described by means of physical and mental work demands. Two factors describing the possibilities for regulating one's own work load were used as indicators for the adjustment of work according to individual capacities. The effect of work stressors on cardiovascular, musculoskeletal, and psychological symptoms was studied in separate analyses, controlling for the relevant disease group. Both chronic diseases and work stressors were related to the occurrence of symptoms. However, stress identified on the basis of symptoms was not only a phenomenon determined by health status. Work stressors and possibilities for regulating one's own work load were systematically related to symptom level.

Age Factors

Work load and individual factors affecting work disability among aging municipal employees.

A cohort of 6165 municipal workers 44 to 58 years of age was followed during 1981-1985. The most impairing work loads were poor work postures and poor physical climate, whereas good possibilities for development at work prevented work disability. Aging particularly increased the incidence of work disability, whereas physical exercise maintained work ability. Among workers who suffered from any cardiovascular disease, a low level of muscular work and a high level of leisure-time physical exercise decreased work disability. Compared with the work ability of active workers, work disability was more linked to individual than to work load factors.

Age Factors

Viral antibodies in multiple sclerosis. A nationwide co-twin study.

Serum viral antibody titers against 21 viruses were studied in 19 of 23 same-sex twin pairs with multiple sclerosis derived from the Finnish Twin Cohort. Thorough neurologic examinations showed two monozygotic pairs to be concordant, whereas all dizygotic pairs were discordant. Special attention was given to measles, mumps, and rubella viruses, against which the antibody levels were determined with the complement fixation, hemagglutination inhibition, hemolysis-ingel, and enzyme immunoassay methods. Epstein-Barr virus antibody levels were determined by enzyme assay. In pairwise comparisons, the measles, mumps, and Epstein-Barr virus-IgG antibody levels were more often elevated in the patients with multiple sclerosis, compared with the healthy co-twins. The same antibody levels were more often above the median in the diseased twin, compared with the healthy twin, but the difference was not significant. No human T-cell lymphotropic virus type I antibodies were found in any of the individuals examined. The total IgG, IgA, and IgM levels did not differ between the diseased and healthy subjects. The HLA types, severity of the disease, and cell-mediated immunity parameters did not influence antibody levels.

Antibodies, Viral

Effect of immunoglobulins on mineral dust-induced production of reactive oxygen metabolites by human macrophages.

Mineral dust-induced production of reactive oxygen metabolites (ROMs) by human monocyte-derived macrophages was investigated using lucigenin-dependent chemiluminescence. Chrysotile asbestos alone caused only weak ROM production by macrophages, but the addition of polyclonal immunoglobulin enhanced the reaction strongly. The phenomenon was seen with 1-, 4-, and 7-day-old cell cultures. Polyclonal immunoglobulin also slightly enhanced the ROM responses induced by amosite, crocidolite, and quartz dust. The enhancing effect could be achieved with several monoclonal immunoglobulins (isolated from the sera of myeloma patients), but IgA and IgG had the strongest effects. We suggest that immunoglobulins may interact with mineral dusts in a "nonimmunological," antigen-independent way and that the so-formed dust-immunoglobulin complexes may amplify the production of ROMs by inflammatory cells. This may explain a number of in vivo phenomena in which immune responses (for instance hypergammaglobulinemia and the presence of autoantibodies) have been shown to relate to the progression of mineral dust-induced pulmonary disease.

Antibodies, Monoclonal

Asbestos fibers induce release of collagenase by human polymorphonuclear leukocytes.

The asbestos fibers chrysotile and crocidolite cause a dose-dependent release of specific granule collagenase by human polymorphonuclear leukocytes (PMNL). Release of azurophil granule elastase was induced by the asbestos fibers at higher concentrations, suggesting that asbestos fibers primarily cause the release of specific granule contents of human PMNL. Wollastonite, a fibrous silicate mineral, causes a weaker collagenase release and no elastase release. The collagenase was released in inactive, latent form. Carboxymethyl cellulose (CMC), an agent known to blunt chrysotile-induced hemolysis and production of reactive oxygen metabolites by human PMNL, specifically inhibits chrysotile-induced release of collagenase. Chrysotile asbestos was found to bind the PMNL serine proteinase cathepsin G. A role of collagenase release, production of reactive oxygen metabolites and cathepsin G binding by chrysotile for the perpetuation of the asbestos-induced alveolitis is suggested.

Asbestos

Asbestos-related malignant mesothelioma: growth, cytology, tumorigenicity and consistent chromosome findings in cell lines from five patients.

Seven mesothelioma cell lines were established from clinical specimens from five patients with asbestos-related malignant pleural mesothelioma. The cells in culture show either epithelial or mixed epithelial/fibrosarcomatous growth with an average doubling time of 30 h. Giant multinucleated cells are common in all the cell lines, as well as long thin microvilli on the cell surfaces. All cell lines were cytokeratin positive and they stained negatively for monocyte-macrophage markers. All seven cell lines and one long-term tissue culture from a sixth mesothelioma patient were characterized cytogenetically. Karyotype analyses revealed complex structural and numerical abnormalities, primarily involving chromosome 1, 4, 5, 6, 7, 8, 9, 11, 12, 13 and 22. An excess of chromosome material of the short arm of chromosome 5 was seen consistently in six cell lines and in the long-term culture. In cell lines from four patients, changes in chromosome 13, mainly monosomy 13, were observed. The marker chromosomes observed in the early passages were conserved and few additional changes appeared in later passages. Six of the cell lines tested for tumorigenicity in athymic nude mice were weakly positive.

Adult

Clinical significance of IgG subclass antibodies to wheat flour antigens in bakers.

We measured the IgG subclass antibody levels to wheat flour in 42 bakers and 20 controls with an enzyme immunoassay. The levels of total IgG, IgG1 IgG2 and IgG4 antibodies were significantly higher in the bakers than in the unexposed controls. The presence of anti-wheat flour IgG subclass antibodies in the bakers was correlated with various clinical variables including IgE levels, duration of asthmatic or rhinitis symptoms, skin prick test response, peripheral blood eosinophil levels, bronchial histamine reactivity and responses to nasal challenge with wheat flour. The IgG subclass antibody levels of the total cohort of bakers did not correlate with any of the measured clinical variables. However, among men specific IgG4 and IgG1 antibody levels correlated negatively with total IgE levels and duration of rhinitis, respectively. We conclude that IgG and IgG subclass levels to wheat flour in bakers reflect exposure, but that it is not related to any specific clinical situation. The exact pathogenic role of these antibodies in the development of occupational asthma and rhinitis is thus not clear.

Adolescent